Work

Refining risk in historically high-risk pediatric B-cell acute lymphoblastic leukemia: response kinetics and outcomes

Year: 2026

Type: article

Abstract: Outcomes in pediatric acute lymphoblastic leukemia (ALL) have improved substantially with contemporary risk-adapted therapy; however, prognosis for historically high-risk subtypes, including KMT2A -rearranged ( KMT2A -r) and hypodiploid ALL, remains uncertain. We performed a post hoc analysis of 28 patients with KMT2A -r ALL and 27 patients with hypodiploid ALL enrolled in the nationwide JCCG ALL-B12 trial to characterize early treatment response, measurable residual disease (MRD) kinetics, transplant exposure, and clinical outcomes under modern therapy. Five-year event-free survival (EFS) and overall survival (OS) were 85.7% and 89.3% for KMT2A -r ALL and 85.2% and 85.2% for hypodiploid ALL, respectively, exceeding historical expectations, although OS remained inferior to favorable subtypes. Clinical behavior was markedly heterogeneous within each subtype. In KMT2A :: AFF1 ALL, patients with prednisolone poor response or persistent MRD had a high risk of relapse despite hematopoietic stem cell transplantation (HSCT). Even among prednisolone good responders, patients with MRD ≥10 -3 at TP1 remained at increased risk of relapse, whereas those with MRD ≥10 -4 but <10 -3 generally showed favorable outcomes. In contrast, non- AFF1 KMT2A -r cases demonstrated rapid MRD clearance and excellent survival. Among hypodiploid ALL, low diploid cases showed excellent outcomes without HSCT. In other hypodiploid subgroups, HSCT was associated with favorable outcomes in many patients; however, some patients with favorable early response achieved long-term survival without transplantation. These findings suggest that historically high-risk ALL subtypes are clinically heterogeneous under contemporary therapy and that early response kinetics may help refine risk stratification and treatment intensification strategies, including indications for HSCT and subtype-directed therapies.

Source: Blood Neoplasia

DOI: 10.1016/j.bneo.2026.100313